NM_000159.4(GCDH):c.1199dup (p.Ile401fs) AND Glutaric aciduria, type 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 22, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001377483.7

Allele description

NM_000159.4(GCDH):c.1199dup (p.Ile401fs)

Gene:

GCDH:glutaryl-CoA dehydrogenase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_000159.4(GCDH):c.1199dup (p.Ile401fs)

HGVS:

NC_000019.10:g.12897819dup
NG_009292.1:g.11660dup
NG_033049.1:g.26454dup
NM_000159.4:c.1199dupMANE SELECT
NM_013976.5:c.1199dup
NP_000150.1:p.Ile401fs
NP_039663.1:p.Ile401fs
NC_000019.9:g.13008632_13008633insT
NC_000019.9:g.13008633dup
NM_000159.2:c.1199dupT
NR_102316.1:n.1362dup
NR_102317.1:n.1580dup

Protein change:

I401fs

Links:

dbSNP: rs1970722328

NCBI 1000 Genomes Browser:

rs1970722328

Molecular consequence:

NM_000159.4:c.1199dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_013976.5:c.1199dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_102316.1:n.1362dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_102317.1:n.1580dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Glutaric aciduria, type 1
Synonyms:: GA I; Glutaryl-CoA dehydrogenase deficiency; Glutaric acidemia type I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009281; MedGen: C0268595; Orphanet: 25; OMIM: 231670

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PPDPFL pancreatic progenitor cell differentiation and proliferation factor like ...
PPDPFL pancreatic progenitor cell differentiation and proliferation factor like [Homo sapiens]
Gene ID:492307

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Gene Links for GEO Profiles (Select 131610331) (1)
Gene
Gene Links for GEO Profiles (Select 131609269) (1)
Gene
SNTG1 syntrophin gamma 1 [Homo sapiens]
SNTG1 syntrophin gamma 1 [Homo sapiens]
Gene ID:54212

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001574824	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9600243, 28492532
SCV002086995	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Apr 8, 2021)	germline	clinical testing
SCV004198744	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 28, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001574824

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 22, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002086995

Natera, Inc.

no assertion criteria provided

Likely pathogenic
(Apr 8, 2021)

germline

clinical testing

SCV004198744

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 28, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13 novel mutations causing glutaric aciduria type I.

Schwartz M, Christensen E, Superti-Furga A, Brandt NJ.

Hum Genet. 1998 Apr;102(4):452-8.

PubMed [citation]

PMID:: 9600243

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001574824.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Ile401Aspfs*18) in the GCDH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the GCDH protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GCDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1066472). This variant disrupts a region of the GCDH protein in which other variant(s) (p.Ala433Glu) have been determined to be pathogenic (PMID: 9600243; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002086995.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004198744.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 9, 2024

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